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Over the past decades, a large number of animal-derived materials have been introduced for several biomedical applications. Surprisingly, the use of plant-based materials has lagged behind. To study the feasibility of plant-derived biomedical materials, we chose flax (Linum usitatissimum). Flax fibers possess excellent physical-mechanical properties, are nonbiodegradable, and there is extensive know-how on weaving/knitting of them. One area where they could be useful is as implantable mesh structures in surgery, in particular for the repair of incisional hernias of the abdominal wall. Starting with a bleached flax thread, a prototype mesh was specifically knitted for this study, and its cytocompatibility was studied in vitro and in vivo. The experimental data revealed that application of flax in surgery first requires a robust method to remove endotoxins and purify the flax fiber. Such a method was developed, and purified meshes did not cause loss of cell viability in vitro. In addition, endotoxins determined using limulus amebocyte lysate test were at acceptable levels. In vivo, the flax meshes showed only mild inflammation, comparable to commercial polypropylene meshes. This study revealed that plant-derived biomaterials can provide a new class of implantable materials that could be used as surgical meshes or for other biomedical applications., (Copyright © 2013 Wiley Periodicals, Inc.)

Bioresorbable coronary vascular scaffolds are about to revolutionize the landscape of interventional cardiology. These scaffolds, consisting of a poly(L-lactic acid) interior and a poly(D,L-lactic acid) surface coating, offer a genuine alternative for metallic coronary stents. Perhaps the only remaining drawback is that monitoring during implantation is limited to two X-ray contrast points. Here, a new approach to make the biodegradable scaffolds entirely radiopaque is explored. A new contrast agent is designed and synthesized. This compound is miscible with poly(D,L-lactic acid) matrix, and nontoxic to multiple cell types. Blends of poly(D,L-lactic acid) and the contrast agent are found to be hemocompatible, noncytotoxic, and radiopaque. The data show that it is possible to manufacture fully radiopaque bioresorbable coronary vascular scaffolds. Whole-stent X-ray visibility helps interventionalists ensure that the scaffold deploys completely. This important advantage may translate into improved safety, accuracy, and clinical performance of cardiac stents., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Vertebroplasty and balloon kyphoplasty are widely used for the augmentation of osteoporosis-induced vertebral compression fractures. Almost invariably, an injectable poly(methyl methacrylate) (PMMA) bone cement that contains a large amount of BaSO(4) particles is used in these procedures. The deleterious effects of this radiopacifier on various properties of PMMA cement have been detailed in the literature. The objective of the present study was therefore to avoid such high levels of inorganic contrast agent and thus to develop an all-polymeric bone cement, for which radiopacity was provided by 60 wt % of an iodine-containing methacrylic copolymer, incorporated into the powder (IO cement), ultimately leading to 6.6 wt % of iodine in the cement. A large array of properties of this cement were determined, ranging from setting time and injectability to fatigue life under fully-reversed tension-compression loading and cytotoxicity, and a comprehensive comparison with a cement containing 30 wt % BaSO(4) in the powder component (BA cement) has been made (11 wt % of Ba in the cement). Statistical analyses of the results showed that, for the majority of the properties, the difference between the means for the two cements was not significant. It is therefore suggested that the IO cement is a suitable alternative to the BA cement for use in the aforementioned procedures., ((c) 2007 Wiley Periodicals, Inc.)

Patients with severe back pain, attributed to a herniation of the nucleus pulposus of the intervertebral disc, can benefit from a replacement of only the nucleus pulposus, provided the annulus fibrosus is still functional. This study investigated four intrinsically radiopaque hydrogel biomaterials, which were designed specifically to replace the herniated nucleus pulposus. The important characteristic of these hydrogels is that they can be visualized entirely with both MRI and X-rays. The materials are based on copolymers of N-vinyl-2-pyrrolidinone (NVP) or 2-hydroxyethyl methacrylate (HEMA) and a radiopacity introducing monomer, 2-(4'-iodobenzoyl)-oxo-ethyl methacrylate (4IEMA). Two of the formulations also contain the chemical crosslinker allyl methacrylate (AMA). Physical-mechanical properties like the water-uptake, biocompatibility, stiffness, and fatigue and creep behavior were studied, while keeping an eye on the intended application. All four materials were designed with 5-6 mass % of iodine to ensure sufficient X-ray visibility between two vertebrae. It was found that the materials display appropriate stiffness and biocompatibility. The crosslinked materials hold most promise as a functional nucleus prosthesis, as they combine these properties also with high water content, fatigue resistance, and recovery after loading.

A series of copolymers, with varying ratio di-methylamino-ethylmethacrylate (DMAEMA) and methyl-methacrylate (MMA), was designed as a potential scale for cytotoxicity. These copolymers were characterized for toxicity of their surface. The surfaces of washed copolymers display increasing toxicity with increasing DMAEMA content. The toxicity was observed for three different cell-types, namely mouse fibroblasts, human endothelial cells and human osteoblast-like cells. With an increasing toxic surface, cell growth was inhibited as was indicated by the proliferation marker Ki-67. Staining for F-actin revealed that with increasing DMAEMA, cells adopted a more and more round morphology, resulting in decreased surface-contact area. Immuno-staining for phospho-tyrosine or vinculin demonstrated gradual loss of focal adhesions on increasingly toxic surfaces. Surprisingly loss of focal adhesions coincided with an increase in paxillin and vinculin protein, indicating cells try compensating for loss of adhesion. This series of copolymers may have potential as a cytotoxicity scale. They provoke cellular responses ranging from highly toxic to completely non-toxic, with some showing intermediate toxicity., (Copyright 2007 Wiley Periodicals, Inc.)

Injectable polymer particles with a diameter in the range of 30-300 microm find applications as a biomaterial in different clinical fields, such as cosmetic surgery, reconstructive surgery, and urology. However, clinical effects tend to disappear after several months, either due to migration of the particles away from the injection site (caused by weak adherence with the surrounding soft tissues) or due to fibrosis (caused by excessive encapsulation of the particles by fibrous tissue). Little is known about the fate of injected microparticles, due to the fact that they are extremely difficult to trace in a noninvasive manner. Design, synthesis, and characterization of new polymeric microspheres with two additional features that can enhance safety and can help to overcome drawbacks of existing products are reported. First, the new microparticles feature clear radio-opacity (X-ray visibility) as they are prepared on the basis of a reactive methacrylic monomer that contains covalently bound iodine. Model experiments reveal that the level of X-ray contrast is sufficient for clinical monitoring; they can be visualized both during the injection and afterward. The particles feature excellent cytocompatibility in vitro and in vivo. Second, a method is explored to functionalize the surface of the particles, for example, through immobilization of collagen. Other extracellular matrix proteins can also be immobilized, and this provides a mechanism to control anchoring of the particles in soft tissue. The results are briefly discussed in the context of improved biomaterials, contemporary X-ray imaging, and control over biomaterial-soft tissue interactions in vivo.

Cardiovascular implants such as vascular grafts fail frequently because they lack genuine blood-compatibility. The blood-contacting surface should simultaneously prevent thrombus formation and promote formation of a confluent endothelial cell layer, to achieve sustained haemostasis. Contact activation and endothelialization are known to be determined by the plasma proteins which adsorb onto virtually all synthetic surfaces almost immediately upon contact with blood. A common approach in blood-compatibility research is, therefore, to use hydrophilic biomaterials, which are sometimes claimed to be "protein-repellent". We report here that, for synthetic polymeric surfaces, hydrophilicity is by no means synonymous to protein-repellency. We discovered that significant amounts of proteins, especially high-density lipoprotein, adsorb to hydrophilic surfaces. Pre-incubation of hydrophilic synthetic surfaces with high-density lipoprotein provides a blood-biomaterial interface, which inhibits thrombin generation and subsequent thrombus formation, and also accommodates overgrowth with a confluent endothelial layer. This approach may open the way to truly functional small-caliber arterial prostheses, and may also be relevant to cardiovascular tissue engineering in which de novo vascular tissues are cultured on or within a biomaterial scaffold.

Radiopaque polymeric microspheres have a potential as new bulking agents for treatment of stress urinary incontinence (SUI). The advantage over existing bulking agents lies in their X-ray visibility in situ; other polymeric bulking agents (e.g., PTFE or silicone rubbers) are practically radiolucent (i.e., incapable of absorbing X-radiation). Radiopacity is useful in practice because of the high spatial accuracy of X-ray imaging. For instance, X-ray fluoroscopy can be used to assess possible migration of the bulking agent over time or to provide guidance in cases in which a second injection of a bulking agent is necessary (repeated treatment of SUI). Biocompatibility of injected radiopaque microspheres was investigated in vivo by using the mouse as a model. Microspheres were injected subcutaneously (9 animals) or intramuscularly (9 animals), and follow-up was 8 days or 3 months. X-ray fluoroscopy gave clear images of the microspheres as an ensemble, and it was found that no migration occurred during 3 months. Histopathology confirmed that all microspheres stayed close to the site of the injection. The microspheres appeared to be well tolerated; only a few giant cells, manifesting a mild inflammatory reaction, were encountered. At 3 months, capillary blood vessels were observed throughout the microsphere beds, and macrophages and fibroblast cells were seen in between the microspheres. This is encouraging with respect to the intended application, although it must be acknowledged that the data refer merely to a mouse model. Further experiments with larger, more representative models (rabbit and goat) are in progress., ((c) 2005 Wiley Periodicals, Inc.)

In all acrylic bone cement formulations in clinical use today, radiopacity is provided by micron-sized particles (typical mean diameter of between about 1 and 2 microm) of either BaSO(4) or ZrO(2). However, a number of research reports have highlighted the fact that these particles have deleterious effects on various properties of the cured cement. Thus, there is interest in alternative radiopacifiers. The present study focuses on one such alternative. Specifically, a cement that contains covalently bound iodine in the powder (herein designated the I-cement) was compared with a commercially available cement of comparable composition (C-ment3), in which radiopacity is provided by BaSO(4) particles (this cement is herein designated the B-cement), on the basis of the strength (sigma(b)), modulus (E(b)), and work-to-fracture (U(b)), under four-point bending, plane-strain fracture toughness (K(IC)), Weibull mean fatigue life, N(WM) (fatigue conditions: +/-15 MPa; 2 Hz), activation energy (Q), and frequency factor (ln Z) for the cement polymerization process (both determined by using differential scanning calorimetry at heating rates of 5, 10, 15, and 20 K min(-1)), and the diffusion coefficient for the absorption of phosphate-buffered saline at 37 degrees C (D). For the B-cement, the values of sigma(b), E(b), U(b), K(IC), N(WM), Q, ln Z, and D were 53 +/- 3 MPa, 3000 +/- 120 MPa, 108 +/- 15 kJ m(-3), 1.67 +/- 0.02 MPa check mark m, 7197 cycles, 243 +/- 17 kJ mol(-1), 87 +/- 6, and (3.15 +/- 0.94) x 10(-12) m(2) s(-1), respectively. For the I-cement, the corresponding values were 58 +/- 5 MPa, 2790 +/- 140 MPa, 118 +/- 45 kJ m(-3), 1.73 +/- 0.11 MPa check mark m, 5520 cycles, 267 +/- 19 kJ mol(-1), 95 +/- 9, and (3.83 +/- 0.25) x 10(-12) m(2) s(-1). For each of the properties of the fully cured cement, except for the rate constant of the polymerization reaction, at 37 degrees C (k'), as estimated from the Q and ln Z results, there is no statistically significant difference between the two cements. k' for the I-cement was about a third that for the B-cement, suggesting that the former cement has a higher thermal stability. The influence of various characteristics of the starting powder (mean particle size, particle size distribution, and morphology) on the properties of the cured cements appears to be complex. When all the present results are considered, there is a clear indication that the I-cement is a viable candidate cement for use in cemented arthroplasties in place of the B-cement., ((c) 2004 Wiley Periodicals, Inc.)

A new composite silicone-metallic prosthesis was tested, studying the potential for respiratory epithelial covering over the biocompatible inner lining, in a rabbit survival model. Seven New Zealand White rabbits underwent near-total excision of their trachea and implantation of a sterile prosthesis. After 2 months, they were sacrificed and the prostheses were retrieved. Specimens were fixed and histologically examined for tissue reaction around the prosthesis, at the anastomotic lines, and particularly for the presence or absence of epithelialization of the inner lumen over the biocompatible surface. All rabbits survived the operation. At 2 months, the outer layer of the prosthesis was consistently covered with fibrosis and neutrophils. The inner layer showed necrotic cells and scant re-epithelialization over the biocompatible lining, up to 5 mm beyond the anastomosis, with no evidence of organized respiratory epithelium in the middle sections. The new prosthesis is a viable temporary solution for airway replacement in rabbits. Granulation tissue was not observed at the anastomosis, and re-epithelialization did occur, but failed to achieve full-length luminal covering. The potential for granulation tissue does not yet make this an ideal long-term solution. Improvements in prosthesis design or biocompatibility are required, and need to be re-evaluated before applicability for chronic use.

A well-known complication in corneal repair surgery is (recurrent) rejection of donor corneal tissue. particularly in patients suffering from an auto-immune disease such as rheumatoid arthritis. Down-regulation of their immune system, by means of drugs, is necessary in order to perform an allograft implantation afterwards. The patient may need a temporary prosthetic cornea while the immune system is inactivated. Recently, NeuroPatch, a mesh-type polyurethane, was used for this purpose. The material exhibits excellent biocompatibility and allows ingrowth of stromal fibroblasts which deposit matrix material into the pores. A serious drawback of NeuroPatch is its non-transparency, which impairs vision. In this work we attempted to develop an improved biomaterial that combines the advantages of NeuroPatch with optical transparency. Based on previous findings that copolymers of hexaethyleneglycolmethacrylate (HEGMA) and butylmethacrylate (BMA), are transparent and well accepted by human corneal epithelial cells, we studied these materials further in detail. (Bruining et al., Bio-Macromolecules 1 (2000) 418) Copolymerizations were studied by means of 1H NMR. The influence of the HEGMA content on hydrophilicity, flexibility and resistance to protein adsorption was studied. The results indicate that materials with a HEGMA content of approximately 20 mol% are potentially useful in corneal repair surgery. These biomaterials meet most of the stringent physical and biological requirements.

Stability tests have been performed on two typical iodine-containing radiopaque poly(methacrylate) copolymers. Material A is a terpolymer of methylmethacrylate (MMA), 2-hydroxyethyl methacrylate (HEMA) and 2-[4-iodobenzoyl]-oxo-ethylmethacrylate (4-IEMA); material B is a copolymer of MMA and 4-IEMA. Cylindrical specimens of material A were implanted subcutaneously and intraperitoneally in Wistar rats. The implants were retrieved after 2 years. Histology showed that the material was well-tolerated. Detailed analysis of the surface of the implants by electron spectroscopy for chemical analysis (ESCA) revealed that the material remained stable. No differences could be detected between the ESCA spectra of the explants, and those of the control specimens, which were from the same synthetic batch and which were stored in dry form during the entire experimental period. Material B was also stable upon irradiation with X-rays in vitro, even at high doses, compared to the clinical situation. Exposure of material B to gamma-radiation, however, was found to lead to structural degradation. This was evident from clear yellowing, and also from the ESCA spectra. The spectra revealed that material B deteriorates during gamma-irradiation through rupture of C-C and or C-O chemical bonds, not via C-I bond disruption. It can be concluded that iodine is tightly bound to these radiopaque biomaterials. This is important with regard to potential applications of these materials as implant biomaterials.